Phase I/II Study of Preoperative Gemcitabine in Combination With Oral Hydroxychloroquine (GcHc) in Subjects With High Risk Stage IIb or III Adenocarcinoma of the Pancreas

Trial Information

Phase I/II Study of Preoperative Gemcitabine in Combination With Oral Hydroxychloroquine (GcHc) in Subjects With High Risk Stage IIb or III Adenocarcinoma of the Pancreas

This is a phase I/II trial designed to assess the safety, tolerability and efficacy of
neoadjuvant oral hydroxychloroquine (Plaquenil®) in combination with FDR gemcitabine in
subjects with high risk IIb or III adenocarcinoma of the pancreas. Eligible subjects will be
administered hydroxychloroquine orally once or twice daily (depending on dose) in
combination with FDR gemcitabine (on days 1 and 15) for 31 days prior to surgical resection.
Dose escalations of hydroxychloroquine will proceed using Storer's Up-and-Down algorithm D.
Subjects will be monitored for side effects and tolerability of the drug. Pre- and
post-treatment PET scans will be the primary means to assess response to therapy. Resected
tumors will also be assessed for evidence of inhibition of autophagy as well as
histopathologic response and margin negative resection and number of positive lymph nodes.

Inclusion Criteria:

- Subjects with biopsy-proven adenocarcinoma of the pancreas

- staged by IIb or greater by by EUS, or tumor greater than 2.6 cm on EUS or
pancreatic protocol helical CT scan demonstrating venous involvement

- Karnofsky performance status >/= 70.

- No active second malignancy except for basal cell carcinoma of the skin

- Normal renal, hepatic, and hematologic function at the time of enrollment as
evidenced by:

- History of allergic reactions or hypersensitivity to the study drugs
(hydroxychloroquine, gemcitabine).

- Other concurrent experimental therapy.

- The effects of HCQ, and gemcitabine on the developing human fetus are unknown. For
this reason women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation. All females of childbearing
potential must have a blood test or urine study within two weeks prior to
registration to rule out pregnancy. Should a woman become pregnant while
participating in this study, she should inform her treating physician immediately. If
a man impregnates a woman while participating in this study, he should inform his
treating physician immediately as well.

- Because patients with immune deficiency are at increased risk of lethal infections
when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded
from the study. For patients receiving combination anti-retroviral therapy, the
potential impact of pharmacokinetic interactions with HCQ and gemcitabine is unknown.
Appropriate studies may be undertaken in patients with HIV and those receiving
combination anti-retroviral therapy in the future.

- Due to the risk of disease exacerbation, patients with porphyria are ineligible.

- Patients with psoriasis are ineligible unless the disease is well controlled and they
are under the care of a specialist who agrees to monitor the patient for
exacerbations.

- Patients requiring the use of enzyme-inducing anti-epileptic medication that
includes: phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are
excluded.

Type of Study:

Study Design:

Outcome Measure:

To establish the safety and tolerability of a novel regimen of pre-operative oral hydroxychloroquine in combination with gemcitabine (GCHC) in patients with high risk stage IIb or III adenocarcinoma of the pancreas

Outcome Description:

The proportion of patients experiencing DLT will be calculated for each dose level, with 90% exact binomial confidence intervals. The dose-toxicity function will be estimated by means of logistic regression, with dose considered as a continuous variable, along with 90% confidence intervals. The dose with estimated probability of toxicity closest to 1/6 will be reported as the recommended Phase II dose.

Outcome Time Frame:

During 31 days of study drug regimen

Safety Issue:

Yes

Principal Investigator

Herbert Zeh, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Institutional Review Board

Study ID:

UPCI 09-122

NCT ID:

NCT01128296

Start Date:

October 2010

Completion Date:

June 2013

Related Keywords:

Pancreatic Cancer

high risk stage IIb or III adenocarcinoma of the pancreas

Adenocarcinoma

Adenocarcinoma, Mucinous

Pancreatic Neoplasms

Name

Location

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